Vapor pressure of nitroglycerin in sublingual molded tablets: implications for stability.

To understand nitroglycerin intertablet migration, vapor pressures of nitroglycerin in tablets were measured using a modified gravimetric Knudsen effusion technique. To supplement the vapor pressure data, adsorption isotherms at 296 degrees K were determined, and tablets were studied by scanning electron microscopy. For conventional tablets (i.e., tablets without stabilizing additives such as polyethylene glycol 400), the nitroglycerin vapor pressure in a tablet is within about 10% of that for pure liquid nitroglycerin, provided the potency is greater than 0.3 mg. Significant capillary condensation in tablets at relative vapor pressures close to unity is demonstrated. Stabilizing additives lower the vapor pressure of nitroglycerin, the magnitude of the effect depending on both the nature of the additive and the additive-nitroglycerin weight ratio. The mechanism of intertablet migration involves capillary condensation. Vapor pressure reduction of about 15%, achieved through the use of an additive, appears sufficient to prevent significant intertablet migration.